Table of Contents

Background

Atherosclerosis develops in a patchy, discontinuous fashion within coronary arteries. Therefore, it is possible to treat the discrete areas of obstruction that most impede coronary blood flow to the myocardium. The mechanical approaches to coronary revascularization fall broadly into two categories: coronary artery bypass grafting surgery (CABG) and catheter-based percutaneous coronary interventions (PCI). Together, these coronary revascularization methods are among the most common major medical procedures performed in North America and Europe.

Coronary bypass surgery and coronary angioplasty (with or without stents) are alternative approaches to mechanical coronary revascularization, so their comparative effectiveness in terms of patient outcomes has been of great interest. The comparative effectiveness of bypass surgery and angioplasty is an open question primarily for those patients for whom either procedure would be technically feasible and whose coronary disease is neither too limited nor too extensive.

CABG is generally preferred for patients with left main coronary artery disease or severe triple-vessel disease with reduced left ventricular function because it has been previously shown in randomized trials to improve survival compared with medical therapy. In contrast, PCI is generally preferred for patients with most forms of single-vessel disease when symptoms warrant coronary revascularization, in light of its lower procedural risk and the evidence that PCI reduces angina and myocardial ischemia in this subset of patients.

The choice between PCI and CABG is most relevant for patients whose coronary artery disease (CAD) lies in between these extremes, namely patients with single-vessel disease of the proximal left anterior descending artery (LAD), most forms of double-vessel CAD, and less extensive forms of triple-vessel CAD. Most randomized controlled clinical trials (RCTs) of angioplasty and surgery have been conducted in this middle segment of the patient population with CAD.

The purpose of this report is to evaluate the evidence for the comparative effectiveness of PCI and CABG in this population of patients with CAD. Specifically, the report addresses the following key questions:

Key Question 1a. In patients with ischemic heart disease and angiographically proven single or multi-vessel disease, what is the effectiveness of PCI compared with CABG in reducing the occurrence of adverse objective outcomes and improving subjective outcomes?

Key Question 1b. Over what period of time are the comparative benefits of PCI and CABG sustained?

Key Question 2. Is there evidence that the comparative effectiveness of PCI and CABG varies based on:

Age, sex, race, or other demographic risk factors?

Coronary disease risk factors, diabetes, or other comorbid disease?

Angiographic-specific factors including, but not limited to, the number of diseased vessels amenable to bypass or stenting, vessel territory of stenoses (e.g., left main or anterior descending coronary arteries, right coronary artery, circumflex coronary artery), diffuse vs. focal stenoses, left ventricular function, or prior revascularization procedures?

CABG-specific factors including, but not limited to, cardiopulmonary bypass mode (normothermic vs. hypothermic), type of cardioplegia used (blood vs. crystalloid), or use of saphenous vein grafts, single or bilateral internal mammary artery grafts, or other types of bypass grafts?

Conclusions

We identified 23 RCTs of PCI vs. CABG that enrolled a total of 9,963 patients. (Descriptions and full names of RCTs are shown in Tables A and B.) The early studies (patient entry 1987-1993) principally used balloon angioplasty as the PCI technique, and the recent studies (1994-2002) principally used stents as the PCI technique. Only one small trial of PCI vs. CABG used drug-eluting stents (Seoul-Hong). The demographic characteristics and cardiac risk factor profiles of trial participants were typical of patients with coronary disease, although only 27 percent of trial patients were women and few trials included patients age 75 and over. Patients with either left main disease, single-vessel disease other than in the proximal LAD, prior CABG, or poor left ventricular function were generally excluded. Among PCI-assigned patients, use of stents and adjunctive medical therapy (e.g., dual antiplatelet therapy) was common in the recent studies but not in the earlier trials conducted when balloon angioplasty was standard. Arterial grafting with the left internal mammary artery was frequently employed in CABG-assigned patients, especially in more recent trials. The quality of most trials was high; all but two trials included randomization methods that were sound and clearly explained, their dropout rates were low, and they performed intention-to-treat analyses.

To assess the extent to which the RCT results are generalizable to the wider population of patients presenting with CAD, we evaluated the results of 96 articles reporting on patients who received either PCI or CABG and were followed in 10 large registries. Overall the quality of the observational studies was high because each enrolled large numbers of subjects who had good followup and adequate descriptions of most key subject characteristics. Among the registries, patients with single-vessel disease were more likely to be selected for PCI, whereas patients with left main or extensive triple-vessel disease or total coronary occlusions were more likely to be selected for CABG.

Short-term/procedural outcomes

For consistency, throughout this document, we present results in the positive frame (e.g., survival rather than mortality, freedom from strokes rather than strokes). We present PCI-CABG survival differences and PCI-CABG differences in freedom from myocardial infarction (MI), stroke, angina, and repeat revascularization such that positive numbers favor PCI and negative numbers favor CABG. Similarly, we present PCI/CABG odds ratios such that ratios greater than 1.0 favor PCI and ratios less than 1.0 favor CABG. In this section, we present the short-term/procedural outcomes which were reported either as “in hospital,” “procedural,” or “within 30 days” of the procedure. Results were statistically homogeneous unless otherwise noted.

Procedural survival. In randomized trials, procedural survival was high for both procedures and did not differ significantly: PCI-CABG procedural survival difference was 0.1 percent (95-percent confidence interval (CI):
-0.3 to +0.6 percent) and PCI/CABG odds ratio for survival of 1.4 (CI: 0.98 to 1.97). There were no significant differences in procedural survival when trials were subdivided into balloon-era and stent-era studies or into single-vessel-disease and multi-vessel-disease patient populations.

In large registries, procedural survival has increased significantly over time. Short-term procedural survival after PCI generally exceeded that of CABG in both earlier and more recent time intervals, however, even after controlling for differences in clinical characteristics.

Freedom from procedural myocardial infarctions. Freedom from procedural MI was not assessed in a consistent fashion across trials of PCI and CABG, and there was significant heterogeneity in this outcome among the randomized trials. The pooled PCI-CABG difference in freedom from procedural MI was small and not statistically significant.

Long-term outcomes

Survival. Long-term survival across all randomized trials between 1 and 5 years of followup was similar in CABG-assigned and PCI-assigned patients, with less than 1-percent absolute PCI-CABG survival difference at each time point. (PCI/CABG odds ratios ranged from 0.94 to 1.13.) None of the differences was statistically significant.

The long-term survival difference between PCI and CABG was significantly different in the older trials that relied on balloon angioplasty, but not in the more recent trials that employed coronary stents. The 5-year survival was higher after CABG in balloon-era trials (PCI-CABG survival difference -2.1 percent, CI: -4.1 to -0.1 percent, p=0.04), whereas 5-year survival did not differ between the procedures in stent-era trials (PCI-CABG survival difference 1.1 percent, CI: -1.4 to +3.7 percent). Stent-era trials included more patients with single-vessel disease, however, and had shorter followup than balloon-era trials.

In large clinical registries, comparative survival after PCI or CABG varied significantly according to the extent of coronary disease. Survival was significantly better after PCI in patients with single-vessel disease that did not involve the proximal LAD, and survival was significantly better after CABG in patients with extensive triple-vessel or left main disease. In analyses from large clinical registries of patients with middle spectrum CAD severity, there was no difference in survival after PCI or CABG.

Freedom from angina. Freedom from angina was significantly greater after CABG than after PCI in randomized trials between 1 and 5 years post-procedure. (PCI-CABG difference in freedom from angina ranged from -5.0 percent to -8.0 percent; PCI/CABG odds ratio ranged from 0.50 to 0.66, p<0.0001 at 1, 3, and 5 years.)

Freedom from repeat revascularization. Freedom from repeat coronary revascularization was significantly greater after CABG than after PCI. (PCI-CABG difference in freedom from repeat revascularization ranged from -23 to -33 percent, PCI/CABG odds ratios ranged from 0.11 to 0.13; p <0.0001 at 1 and 5 years.) The gap between PCI and CABG in repeat revascularization procedures narrowed in more recent trials that used coronary stents. Nevertheless, patients undergoing PCI with stents required repeat procedures significantly more often than patients undergoing CABG.

Freedom from myocardial infarction. The PCI-CABG difference in freedom from MI was small, less than 1 percent (PCI/CABG odds ratios ranged from 0.87 to 0.92), between 1 and 5 years after the procedure and did not achieve statistical significance at any time point.

Quality of life. Eleven randomized trials reported quality-of-life data using a variety of different measures. In general, quality-of-life scores improved to a significantly greater extent after CABG than after PCI between 6 months and 3 years of followup but equalized thereafter. The degree of improvement in quality of life was correlated with relief of angina.

Cost. The methods of cost determination varied among trials and countries, yet 9 of the 10 RCTs found that the initially lower cost among PCI-assigned patients narrowed substantially over followup. In medium- to long-term followup, PCI-assigned patients had only modestly lower costs (roughly 5 percent) than CABG-assigned patients. This pattern of progressively narrowing cost differences was evident both in trials employing balloon angioplasty and in trials using coronary stents.

Comparative effectiveness by patient demographics

In contrast to the fairly robust evidence concerning overall clinical outcomes, there was much less evidence from randomized trials to gauge whether the comparative effectiveness of CABG and PCI varies according to patient or provider characteristics. Most clinical trials have not reported outcomes in key subgroups, and most have reported only survival, not other outcomes. The most extensively examined subgroup (patients with diabetes) was reported by only 7 of 23 randomized trials. Furthermore, the selection of patients and providers to participate in trials narrowed the range of clinical characteristics and reduced the statistical power to detect variations. For example, most patients in RCTs had preserved left ventricular function, so variations in the efficacy of PCI and CABG according to ventricular function would be difficult to detect. Nevertheless, some conclusions can be drawn from the evidence provided by randomized trials and large registries.

Age. Older patients had more procedural complications from both PCI and CABG, especially stroke. Patients aged 65 years and older had lower long-term survival compared with younger patients. The survival difference between PCI and CABG at 7 years in the BARI trial did not significantly favor CABG in the older patients (-4.7 percent PCI-CABG survival difference) to a greater extent than in the younger patients (-2.8 percent PCI-CABG survival difference). Older patients had more freedom from angina, however, and more freedom from repeat revascularization procedures. The randomized trials enrolled very few patients 75 years of age and over, so conclusions about the comparative effectiveness of PCI and CABG cannot be made for very old patients.

Gender. Roughly 27 percent of the patients in randomized trials were women, and their outcomes were similar to those among men in the trials that examined outcomes by gender. In the BARI trial, women had lower overall survival than men with each procedure, but the PCI-CABG survival difference in women was similar to that in men. In the pooled data from four stent-era trials (ARTS, ERACI-II, MASS-II, SoS), women had clinical outcomes relatively similar to those of men.

Race. Outcomes after PCI and CABG according to race were analyzed only by the BARI trial and registry, which found African-American patients had significantly lower overall survival, irrespective of treatment with PCI or CABG.

Comparative effectiveness by comorbidities

Diabetes. Survival at 1 and 5 years in patients with diabetes was reported by six trials (Figure A). The BARI trial reported a significant survival advantage for patients with diabetes assigned to CABG: 5-year survival of 80 percent with CABG vs. 65 percent with PCI. None of the other trials found as dramatic a difference in survival between patients with and without diabetes. In the EAST trial, for example, the 59 patients with treated diabetes had slightly better survival in the PCI arm at 3 years, equivalent survival at 5 years, and slightly better survival in the CABG arm at 8 years. Among the 62 patients with diabetes in the RITA trial, however, only 2 of the 29 PCI patients died, compared with 8 of the 33 CABG patients. Overall, the survival difference between PCI and CABG was not significantly different among patients with diabetes (Figure A); the pooled PCI-CABG survival difference was -0.8 percent at 5 years, but the confidence limits were very wide, from -8.3 to +6.6 percent (PCI/CABG odds ratio 0.87; CI: 0.51 to 1.49).

Obesity. In general, obesity was not consistently associated with significant differences in comparative effectiveness of PCI and CABG in the two trials that reported outcomes by body mass index. Overall rates of survival, freedom from MI, and freedom from stroke were not affected by body mass index in the ARTS trial. Survival in the BARI trial was decreased in patients with either a very low (<20) or a very high (Â³35) body mass index.

Other comorbidities. Outcomes according to hypertension, tobacco use, renal dysfunction, and vascular disease were not generally reported by randomized trials.

Comparative effectiveness by angiographic factors

Extent of disease. There was no significant difference in the comparative survival benefit when randomized trials were subdivided into those enrolling patients with single-vessel proximal LAD disease and those enrolling patients with multi-vessel disease (Figure B). In the RITA trial, the survival difference between PCI and CABG was comparable in patients with single-vessel disease and multi-vessel disease (mostly two-vessel disease).

In the randomized trials that enrolled patients with multi-vessel disease, the survival difference between CABG and PCI was greater among patients with three-vessel disease than among patients with two-vessel disease but did not achieve statistical significance. The randomized trials generally excluded patients with extensive coronary disease. Accordingly, comparative efficacy of CABG and PCI according to variations in coronary anatomy could not be fully tested.

In large clinical registries, comparative survival after PCI or CABG varied significantly with the extent of coronary disease, with better survival after PCI in patients with the least extensive coronary disease and better survival after CABG in patients with the most extensive disease.

Left ventricular function. Most trials comparing PCI and CABG randomized patients with relatively preserved left ventricular function and a low prevalence of heart failure. The limited range of ejection fractions within the trials precludes a stringent test of whether the comparative effectiveness of PCI and CABG varies according to left ventricular function. Only the BARI and AWESOME trials reported specific analyses: they found no significant differences in the comparative efficacy of PCI and CABG according to the level of left ventricular function.

Comparative effectiveness by CABG-specific factors

Use of minimally invasive techniques. “Minimally invasive” surgery, which is performed through a small throracotomy incision on a beating heart, was compared with PCI in eight small randomized trials. These trials enrolled patients with single-vessel proximal LAD disease (predominantly or exclusively) and generally used PCI with stents as the comparator. These trials showed no significant differences in survival between PCI and CABG over a relatively short followup period.

Use of internal mammary arteries. Standard CABG was used in all trials that enrolled patients with multi-vessel disease, with variable use of left internal mammary grafting, ranging from a low of 37 percent in the early GABI study to over 90 percent in the more recent ARTS, MASS-II, and SoS studies. In a meta-regression, the 1-year survival advantage for CABG vs. PCI increased along with the proportion of internal mammary artery grafts used, but this trend was not statistically significant and not evident at 5 years.

Comparative effectiveness by clinical presentation

Three randomized trials (ARTS, BARI, and SoS) examined the outcomes of patients according to their clinical presentation. Comparative survival after PCI and CABG was not consistently different between patients with stable or unstable angina. The randomized trials generally excluded patients with acute myocardial infarction, severe congestive heart failure, or cardiogenic shock, so no conclusions about the comparative efficacy of PCI and CABG can be drawn for these patient subgroups.

Comparative effectiveness and use of adjunctive medical therapies

The RCTs did not report comparative effectiveness data based on the use of adjunctive medical therapy for PCI or CABG. It is uncertain whether patients who have undergone CABG are as likely as patients who have undergone PCI to comply with recommendations for long-term use of aspirin, beta-blockers, angiotensin-converting enzyme inhibitors, and statins. There is relatively little evidence on this question from randomized trials; however, the Duke Database, a large observational registry of patients receiving both procedures, reports relatively similar use of evidence-based therapies after PCI and CABG.

Comparative effectiveness and volume-outcome relationship

There was considerable evidence that procedural outcomes of both CABG and PCI were significantly worse in low-volume hospitals and with low-volume operators. This relationship remained significant for PCI, even as procedural risk has been reduced by the availability of coronary stents and adjunctive therapy. While none of these studies were randomized and causality is uncertain, these findings are consistent with a large body of literature demonstrating a relationship between the volume of patients treated and short-term survival for a wide variety of procedures. The magnitude of association of procedural outcomes with volume of PCI and CABG may be only modest, however, at least among sufficiently experienced centers and operators.

Comparative effectiveness and prior revascularization

Most randomized trials excluded patients with prior CABG, but one randomized trial and several clinical registries have compared PCI with re-do CABG in patients with a prior CABG. In the AWESOME trial, 142 patients with prior CABG were randomized to either re-do CABG (75 patients) or PCI (67 patients). While procedural survival was significantly lower in the patients assigned to CABG (92 vs. 100 percent), 3-year survival did not differ significantly. A similar pattern has been reported by large clinical registry studies from Cleveland, Emory, and Kansas City: procedural mortality was higher for re-do CABG than for PCI, but survival at 5 to 6 years of followup did not differ significantly.

Remaining Issues

This comprehensive review of the comparative effectiveness of PCI and CABG identified numerous gaps in evidence that would be suitable for future research. The paucity of published analyses of PCI and CABG outcomes according to patient characteristics strongly suggests the value of a collaborative pooling of individual patient-level data from the randomized trials to (a) enhance statistical power to identify subgroup effects and (b) reduce publication bias by including data from all trials. A collaboration of four stent trials (ARTS, ERACI-II, MASS-II, and SoS) has pooled 1-year outcomes and provided useful short-term analysis in key subgroups. The planned extension of this collaborative pooling to include 5-year followup data should be very informative.

A more extensive collaborative study to pool individual patient data from both balloon-era and stent-era trials would provide additional advantages. First, the number of patients and outcome events would be greatly increased, thereby improving statistical power even further in patient subgroups. Second, more direct assessments of the impact of stents on the comparative effectiveness of PCI and CABG would be feasible, as well as assessment of whether relative efficacy changes over extended followup.

Further research on the association of procedure volume with outcome should examine additional outcome measures, both short term (e.g., nonfatal myocardial infarction, completeness of revascularization) and long term (e.g., survival, angina relief, freedom from repeat procedures), preferably in large patient cohorts using contemporaneous CABG and PCI and applying the same analytic methods. Development of evidence-based process measures for PCI and CABG would facilitate efforts to improve quality of care and might provide better performance measures than procedure volume. However, research is required to understand the relative ability of structural measures (e.g., volume) and process measures to predict institutions or physicians with low-quality CABG and PCI outcomes.

Further clinical trials are also needed to assess whether the availability of drug-coated stents has affected the comparative efficacy of PCI and CABG. Such trials are particularly warranted, as pooled studies suggest that rates of survival and MI are not different between bare metal stents and drug-coated stents over medium-term followup. Recent safety concerns about drug-coated stents emphasize the need for extended followup and trials large enough to detect clinically meaningful differences in outcomes. Furthermore, the procedural risk of CABG in large registries has also declined progressively over time, indicating that both CABG and PCI methods continue to evolve. Several trials to compare contemporary CABG with PCI using drug-coated stents, including the large FREEDOM (NCT 00086540) and SYNTAX trials (NCT 00114972), are currently underway and should be complete in 2012.1

1 NCT numbers are National Clinical Trial numbers, which the National Institues of Health assigns to trials for tracking purposes.

A medium-sized trial of 450 patients with MVD conducted by the same Argentine group that organized ERACI-I. The trial used bare metal stents and was one of four trials that participated in the primary data pooling project.

A small, single-center Brazilian trial that used three treatment options for patients with single-vessel proximal LAD disease. (Only outcomes in patients assigned to PCI or CABG were used in this report.)

A medium-sized Brazilian trial of 408 patients with MVD conducted by the same investigators as the MASS-I trial. This study used bare-metal stents and was one of four trials that contributed to the primary data pooling project for stent trials.

A small, single-center German trial of 44 high-risk patients with left main or left main equivalent disease randomized to PCI supported by retroinfusion of the anterior cardiac vein or to bypass surgery.

Overall survival in RCTs was slightly higher after CABG than after PCI between 1 and 5 years of followup, but the absolute PCI-CABG survival difference was small at each time point (less than 1%) and not statistically significant.